ArticleBlood2020
Complement activity and complement regulatory gene mutations are associated with thrombosis in APS and CAPS.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 3 of them syntheses that pooled it.
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Who cites it
121 citing papers in PubMed, 3 syntheses or guidelines pooled it, 222 citations in OpenAlex.
- Pooled it
- A multidimensional analysis of neuropsychiatric lupus: clinical, biological and imaging insights from systematic evidence.Frontiers in immunology · 2026Pooled it
- Update in Hyperferritinemic Syndromes: Recognition and Management - A Scoping Review.The Brown journal of hospital medicine · 2022Pooled it
- Antiphospholipid antibodies and cardiovascular thrombosis.Nature reviews. Cardiology · 2026Review
- Methodology of the development of the EULAR Antiphospholipid Syndrome Disease Activity Score (EAPSDAS).EULAR rheumatology open · 2026Article
- The evolving landscape of complement therapeutics in rheumatology.Annals of the rheumatic diseases · 2026Review
- In vivo targeting of open prothrombin with the monoclonal antibody POmAb results in anticoagulation without excessive bleeding.Journal of thrombosis and haemostasis : JTH · 2026Article
- Unveiling the molecular impact of pulmonary embolism on the right ventricle: a multi-layer transcriptomic study in a porcine model.Molecular and cellular biochemistry · 2026Article
- MUC4 mutations promote a thrombotic phenotype in patients with paroxysmal nocturnal haemoglobinuria by increasing the deposition of terminal complement.Clinical and translational medicine · 2026Article
- Case Report: Avermectin poisoning-associated hemolytic uremic syndrome.Frontiers in immunology · 2026Article
- Update in the diagnosis of complement-mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome.Hematology. American Society of Hematology. Education Program · 2025Review
- Article
- Complement activation in secondary thrombotic microangiopathies.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Activated Complement System's Impact in Antiphospholipid Syndrome Thrombosis: From Pathophysiology to Treatment.Journal of clinical medicine · 2025Review
- Cardiovascular Risk in Autoimmune Diseases: Mechanisms, Management, and Emerging Evidence.Cureus · 2025Review
- Thrombin generation test as a useful tool for improving disease severity stratification in antiphospholipid syndrome.RMD open · 2025Article
- The complement system in autoimmune diseases: pathogenesis, diagnostic markers, and therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Prevalence and Risk Factors of Acute Ischemic Stroke in Patients with Antiphospholipid Syndrome: A Retrospective Monocenter Analysis.Journal of cardiovascular development and disease · 2025Article
- Perspective on Renal Involvement in Antiphospholipid Syndrome: Implications for Diagnosis, Pathogenesis, and Treatment.Journal of clinical medicine · 2025Review
- Avascular Necrosis of the Femoral Head in Patients with Antiphospholipid Syndrome: A Case Series.Hematology reports · 2025Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies, including anti-β2-glycoprotein-I (anti-β2GPI), that are considered central to APS pathogenesis. Based on animal studies showing a role of complement in APS-related clinical events, we used the modified Ham (mHam) assay (complement-dependent cell killing) and cell-surface deposition of C5b-9 to test the hypothesis that complement activation is associated with thrombotic events in APS. A positive mHam (and corresponding C5b-9 deposition) were present in 85.7% of catastrophic APS (CAPS), 35.6% of APS (and 68.5% of samples collected within 1 year of thrombosis), and only 6.8% of systemic lupus erythematosus (SLE) sera. A positive mHam assay was associated with triple positivity (for lupus anticoagulant, anticardiolipin, and anti-β2GPI antibodies) and recurrent thrombosis. Patient-derived anti-β2GPI antibodies also induced C5b-9 deposition, which was blocked completely by an anti-C5 monoclonal antibody, but not by a factor D inhibitor, indicating that complement activation by anti-β2GPI antibodies occurs primarily through the classical complement pathway. Finally, patients with CAPS have high rates of rare germline variants in complement regulatory genes (60%), compared with patients with APS (21.8%) or SLE (28.6%) or normal controls (23.3%), and have mutations at a rate similar to that of patients with atypical hemolytic uremic syndrome (51.5%). Taken together, our data suggest that anti-β2GPI antibodies activate complement and contribute to thrombosis in APS, whereas patients with CAPS have underlying mutations in complement regulatory genes that serve as a "second hit," leading to uncontrolled complement activation and a more severe thrombotic phenotype.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.